Fecal Transplant Capsules Nearly Double Immunotherapy Response Rates Across Three Cancer Types in Phase I/II Trials
Two companion trials published in Nature Medicine show oral FMT capsules raised immunotherapy response rates to 80% in lung cancer and 75% in melanoma, while reducing toxic side effects in kidney cancer.
Overview
Two companion clinical trials published in Nature Medicine in January 2026 report that oral fecal microbiota transplant (FMT) capsules, when combined with immune checkpoint inhibitors, produced markedly higher response rates in patients with lung cancer, melanoma, and kidney cancer than immunotherapy alone typically achieves. The studies — PERFORM (Phase I) and FMT-LUMINate (Phase II) — used the same standardized capsule product, LND101, developed by the Lawson Research Institute in London, Ontario.
The results add to a growing body of evidence that manipulating the gut microbiome can meaningfully alter how tumors respond to immunotherapy, a treatment paradigm that has reshaped oncology over the past decade but still fails to help the majority of patients with certain cancer types.
What We Know
The FMT-LUMINate trial was a multicenter, open-label Phase II study that enrolled 40 patients in two cohorts: 20 with non-small cell lung cancer (NSCLC) who received FMT plus anti-PD-1 therapy, and 20 with melanoma who received FMT plus dual immune checkpoint inhibition (anti-PD-1 and anti-CTLA-4). Each patient received a single FMT via oral capsules before starting immunotherapy.
The objective response rate in the NSCLC cohort reached 80% (16 of 20 patients), compared to the 39-45% typically observed with immunotherapy alone in this population. In the melanoma cohort, 75% of patients (15 of 20) responded, against a historical baseline of 50-58% for dual checkpoint inhibitor therapy. An independent data and safety monitoring committee found FMT to be safe in both cohorts, with no grade 3 or higher adverse events in the NSCLC group. In the melanoma cohort, 65% of patients experienced grade 3 or higher adverse events, consistent with the known toxicity profile of dual checkpoint inhibition rather than the FMT itself.
The companion PERFORM trial, a Phase I study, enrolled 20 treatment-naive patients with metastatic renal cell carcinoma at the Verspeeten Family Cancer Centre. These patients received LND101 capsules combined with standard immunotherapy regimens — primarily ipilimumab plus nivolumab (16 patients), with smaller groups receiving pembrolizumab plus axitinib or pembrolizumab plus lenvatinib. The trial met its primary safety endpoint: while 50% of patients experienced grade 3 immune-related adverse events, there were no serious FMT-related toxicities and no grade 4 or 5 events. The kidney cancer arm focused primarily on toxicity reduction rather than response rate enhancement, addressing the significant problem of colitis and diarrhea that forces some patients to discontinue immunotherapy prematurely.
The Mechanism
Microbiome analysis from the FMT-LUMINate trial revealed that the therapeutic benefit may stem not from introducing beneficial bacteria but from eliminating harmful ones. According to the study findings, responders exhibited significantly greater loss of baseline bacterial species compared to non-responders, with frequent depletion of Enterocloster citroniae, E. lavalensis, and Clostridium innocuum. Responders developed a distinct post-FMT gut microbiome composition independent of donor-recipient similarity or strain-level engraftment, suggesting that the transplant works by disrupting immunosuppressive microbial populations rather than by colonizing the gut with specific beneficial strains.
What We Don’t Know
Both trials were small, with 20 patients per cohort, and lacked placebo controls — a limitation the researchers acknowledge. Phase III randomized controlled trials will be needed to confirm whether the response rate improvements hold in larger populations. The pan-Canadian Canbiome2 randomized controlled trial is reportedly underway to address this gap.
It remains unclear which patients are most likely to benefit from FMT prior to immunotherapy, and whether baseline microbiome composition could serve as a biomarker for patient selection. The durability of the response improvements has not yet been fully characterized, and long-term follow-up data from both trials are pending.
The LND101 capsules are processed from healthy donor stool, raising questions about standardization and scalability. While the Lawson Research Institute reports that production can be scaled, the relationship between donor microbiome characteristics and recipient outcomes is not yet well understood.
Research into FMT for cancer immunotherapy is also expanding beyond these three cancer types. Studies in pancreatic cancer and triple-negative breast cancer are reportedly in progress, though no results from those efforts have been published.
Analysis
The PERFORM and FMT-LUMINate trials arrive at a moment when the microbiome therapeutics field is gaining clinical traction after years of preclinical promise. As previously reported, a separate Phase III trial — BioFront — is enrolling over 700 kidney cancer patients to test CBM588, a defined bacterial supplement, alongside checkpoint inhibitors. Where CBM588 represents a targeted single-strain approach, the FMT capsules tested in PERFORM and FMT-LUMINate take a broader, whole-microbiome strategy. The mechanistic finding that benefit may derive from eliminating harmful bacteria rather than introducing helpful ones adds nuance to the field’s understanding and could influence the design of next-generation microbiome therapies.
If the response rates observed in FMT-LUMINate are confirmed in larger, randomized studies, the implications would be substantial. Lung cancer remains the leading cause of cancer death worldwide, and only about 20-45% of NSCLC patients respond to current immunotherapy regimens. A safe, scalable intervention that could push response rates to 80% would represent one of the most significant advances in lung cancer treatment in recent years.